tbuckley/cabot-search huggingface dataset:
Abstract 11162: Low Left Atrial Appendage Flow Velocity Predicts Treatment Failure in Patients With Left Atrial Thrombi: Insight From the LAT Trial
Authors: Masato Okada, Nobuaki Tanaka, Koji Tanaka, Yuko Hirao, ATSUNORI OKAMURA, Katsuomi Iwakura, Yasuyuki Egami, masaharu masuda, Akihiro Sunaga, Shungo Hikoso, Koichi Inoue, Yasushi Sakata
Journal: Circulation (2022)

Background: Blood stasis is one of the important pathogeneses in the formation of left atrial (LA) thrombi. The LA appendage peak flow velocity (LAAV) is an established quantitative parameter for estimating the thromboembolic risk. However, it remains unknown whether the LAAV affects the successful resolution of LA thrombi even after prescribing an appropriate oral-anticoagulation treatment. Purpose: To evaluate whether the LAAV is associated with successful resolution of LA thrombi. Methods: The analysis was performed from the LAT trial, a multicenter observational study investigating the outcomes of silent LA thrombi detected by trans-esophageal echocardiography (TEE) or computed tomography. Management of oral anticoagulants was at the physician’s discretion, and resolution of LA thrombi was checked by follow-up TEE. Of 297 patients registered in the trial, we enrolled 236 patients (median age, 69 years; 28% female; 100% atrial fibrillation) whose baseline LAAV data was available in this study. Results: The prescription rates of oral-anticoagulants at baseline and the final follow-up were 83.5% and 93.6%, respectively (p = 0.002). During a median follow-up of 387 (interquartile range, 367-414) days after the thrombi detection, LA thrombi successfully resolved in 145 (61.4%) patients by altering the oral anticoagulants. Patients with resolved LA thrombi had a higher baseline LAAV than those without (28.4 ± 18.5 vs. 19.8 ± 9.3 cm/s, p &lt; 0.001). A receiver operating curve analysis revealed that the best cut-off value for predicting treatment success or failure was 25 cm/s (area under the curve: 0.651, p &lt; 0.001). After adjusting for age, gender, body mass index, heart failure, and warfarin use, an LAAV ≤ 25 cm/s was a significant predictor of failed resolution of LA thrombi (hazard ratio, 1.54; 95% confidence interval, 1.09-2.18; p = 0.015). Conclusions: In the LAT trial, one third of patients failed thrombolysis even 1 year after identifying silent LA thrombi. An LAAV ≤ 25 cm/s at baseline independently predicted treatment failure with oral anticoagulants.
Abstract 12299: Impact of Diabetes Mellitus on Clinical Outcomes in Patients With Minimal and Intermediate Coronary Artery Disease Diagnosed by Coronary Ct Angiography
Authors: Sung Woo Cho, Dong-Gil Kim, Ji-Won Hwang, Joon-Hyung Doh, Jae-Jin Kwak, June Namgung, Sung Yun Lee, Sung Uk Kwon
Journal: Circulation (2022)

Introduction: Diabetes mellitus (DM) is the most important risk factor for coronary artery disease (CAD) progression and prognosis. The DM patients with normal coronary artery on coronary CT angiography (CCTA) had good prognosis, however the prognosis of minimal and intermediate CAD was not fully elucidated. The aim of this study was to investigate the impact of DM on clinical outcomes in patients with minimal and intermediate CAD diagnosed by CCTA. Methods: A total of 6014 patients underwent CCTA were prospectively enrolled and the 1126 patients with minimal and intermediate CAD were analyzed. Patients were categorized according to maximal severity of coronary artery stenosis: minimal CAD (31 to 50%) and intermediate CAD (51 to 70%). The primary outcome was major adverse cardiac events (MACE) including all-cause death, non-fatal myocardial infarction, coronary revascularization, or cardiac hospitalization. Results: Nine hundred eighty-five patients had minimal CAD and 141 patients had intermediate CAD. The DM patients were 307 (31.2%) in the minimal CAD group and 52 (36.9%) in the intermediate CAD group. During the follow-up period (median 18.9 months [interquartile range: 7.8 to 34.6 months]), there is no significant difference of the risk of MACE between the non-DM and DM patients in the minimal CAD group (26.9% vs. 32.8%; adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.74-1.49; p =0.79). However, compared with the non-DM patients, the DM patients significantly increased the risk of MACE in the intermediate CAD group (36.5% vs. 63.2%; adjusted HR, 2.37; 95% CI, 1.18-4.77; p =0.02). Conclusions: The prognosis of the DM patients was similar with the non-DM patients in the minimal CAD group. However, the DM patients had worse clinical outcomes compared with the non-DM patients in the intermediate CAD group.
Abstract 12168: Pi3kγ is a Key Modulator of Cardiac Metabolism Rewiring Occurring in Doxorubicin-Treated Mice
Authors: Michele Russo, Rebecca Priolo, Giulia Guerra, Chiara Riganti, Emilio Hirsch, Alessandra Ghigo
Journal: Circulation (2022)

Introduction: Doxorubicin (DOX) is a potent chemotherapeutic drug, whose use is hampered by the onset of long-term cardiotoxicity and lack of effective therapeutic approaches. Recently, metabolic perturbations have emerged as an early predictor factor of cardiac dysfunction, but how DOX affects cardiac metabolism is still unknown. We have previously demonstrated that phosphoinositide 3-kinase γ (PI3Kγ) is a major driver of DOX-evoked cardiotoxicity through mitophagy inhibition and accumulation of dysfunctional mitochondria. Hypothesis: Here we sought to explore the role of PI3Kγ in modulating cardiac metabolism upon DOX administration. Methods: Metabolomic analysis, glycolysis and oxidative phosphorylation were measured in whole hearts from wild-type (WT) and knock-in mice expressing a kinase-inactive PI3Kγ (kinase-dead; KD) treated with DOX (4 mg/kg on day 0, 7 and 14). Similar analyses were performed in WT and KD hearts infected with AAV9-shATG7 to explore the role of autophagy. Moreover, glucose uptake and GLUT-4 expression on the plasma membrane were measured in WT and KD neonatal mouse cardiomyocytes (NMCs) exposed to 1μM DOX. Results: Metabolomic analysis revealed an increased level of succinate and malic acid in DOX-treated hearts, suggesting defects in the TCA cycle. In agreement, DOX promotes the accumulation of metabolites normally catabolised in the TCA cycle, such as aminoacids and pyruvate, indicating a severe mitochondria dysfunction. Accordingly, fatty acid oxidation and electron transport chain activity were impaired in DOX-treated hearts at day 3 and exacerbated at day 42 after DOX. At the same time, glycolysis was upregulated. These changes were prevented in KD animals. Interestingly, upon autophagy inhibition, KD mice lost their cardioprotection at the mitochondrial level, but they still failed to upregulate glycolysis. This suggests a new autophagy-independent mechanism through which PI3Kγ regulates glucose utilisation. In agreement with the pharmacological and genetic inhibition of PI3Kγ abrogates glucose uptake in NMCs and normalises the plasma membrane exposure of GLUT-4. Conclusions: Overall, these results promote PI3Kγ as a master regulator of metabolic rewiring occurring in DOX-treated cardiomyocytes.
Abstract 11920: Positive Hiv Status Increases Length of Stay And Cost of Hospitalization Among Hospitalized Patients With Acute Myocardial Infarction and Heart Failure: An Analysis of National Inpatient Sample 2016 to 2019
Authors: Saeed Shoar, Samin K Sharma
Journal: Circulation (2022)

Introduction: Due to dramatic advance in the development of highly active antiretroviral therapy, patients living with human immunodeficiency virus (HIV) (PLWH) have gained a near-normal life expectancy. As a result, cardiovascular diseases are now the most common causes of mortality among PLWH. Objectives: We aimed to investigate if HIV positive status affect the outcomes of PLWH hospitalized with acute myocardial infarction (AMI) or heart failure (HF) in the United States. Methods: Using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), we queried the national inpatient sample database to identify admission cases with AMI or HF between 2016 and 2019. Then, we stratified the AMI and HF cases according to their HIV status. Weighted data was analyzed to compare mortality rate, frequency of home disposition (HD), length of stay, and total hospital charges between HIV positive and HIV negative patients for AMI and HF admission cases. Results: Data pertaining to a total of 28,484,087 admissions was analyzed. Of this, there were 896,702 cases of AMI and 4,154,918 cases of HF. HIV status was positive in 0.24% and 0.32% of AMI and HF patients, respectively. Conclusion: HIV positive status is associated with a longer length of stay and total hospital charged among hospitalized patients with AMI or HF. While PLWH admitted with AMI have a higher mortality rate than HIV negative counterparts, the HIV status does not seem to impact the outcome of HF patients. Additionally, PLWH seem to be more frequently discharged home than HIV negative patients.
Abstract 12042: A Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac LDLR Expression
Authors: Monique M Williams, Jose Manuel Condor Capcha, Camila Iansen Irion, Grace Seo, Guerline Lambert, Ali Kamiar, Rosemeire M Kanashiro-Takeuchi, Lauro Takeuchi, Ali Saad, Armando J Mendez, Keith A Webster, Jeffrey J Goldberger, Joshua M Hare, Lina A Shehadeh
Journal: Circulation (2022)

Background: HFpEF prevalence has surpassed that of HFrEF. Elevated accumulation of myocardial lipids is a prominent feature of HFpEF patients and the gene for lipoprotein lipase (LPL) in cardiac biopsies is decreased compared with HFrEF or healthy controls. Poloxamer-407 (p407) induces hyperlipidemia by blocking LPL and increasing plasma triglycerides (TG) and LDL cholesterol. We hypothesized that hyperlipidemia driven by p407 and overexpression (OE) of cardiac LDLR in mice mimics a subset of human HFpEF. Methods: WT-129 mice were subject to 4 wks of biweekly i.p. p407-injections with or without a single i.v. injection of AAV9-cTnT-LDLR (n=31); AAV9-cTnT-Luciferase control (n=11), or single i.v. injection with AAV9-cTnT-LDLR alone (n=10). Treatment groups were compared to an untreated group (n=26). Echo, blood pressure (BP), whole-body plethysmography (WBP), ECG telemetry, activity wheel monitoring (AWM), biochemical tests, and histological changes were assessed at 4-8 wks. Results: At 4 wks, p407 and LDLR OE led to diastolic dysfunction (DD) (prolonged IVRT, decreased E/A (p&lt;0.05 and p&lt;0.001 respectively)), preserved EF and increased LV wall thickness (LVID and LVAW, p&lt;0.0001). BP and WBP were normal at 4 wks but respiration (breaths per minute) decreased at 8 wks (p&lt;0.01). ECG and AWM respectively indicated heart block and decreased exercise activity (p&lt;0.001). With the double treatment, total cholesterol increased in heart, skeletal muscle and liver (p&lt;0.05), while TG was decreased only in hearts (p&lt;0.001) and liver (p&lt;0.05). Double treatment also promoted elevated myocardial lipids, fibrosis, increased Wet/Dry lung (p&lt;0.001) and HW/BW (p&lt;0.05). Xanthelasma, ascites, and cardiac ischemia were noted in the double and single, p407 + luciferase groups. Sudden death (SD) occurred between 6-12 wks in double and p407+Luciferase treatment groups. Conclusion: We present a unique model of early onset, rapidly evolving HFpEF where double treatment mice acquire DD, arrhythmia, cardiac hypertrophy, fibrosis, pulmonary congestion, exercise intolerance, and preserved EF in the absence of obesity, HTN, CKD or DM. The model may represent a subset of HFpEF wherein hyperlipidemia drives a severe phenotype with SD as a prominent endpoint.
Abstract 12644: Multiple Spontaneous Coronary Artery Dissections in a Middle-Aged Man With Acute Chest Pain
Authors: arushi sharma, Nitish Sharma, Sai Vikram Alampoondi Venkatarmanan, neeta shah
Journal: Circulation (2022)

Introduction: Previously considered rare, spontaneous coronary artery dissection (SCAD) has emerged as an important cause of chest pain, acute coronary syndrome, and sudden cardiac death. Due to hormonal factors, SCAD often affects seemingly healthy women. SCAD in men remains little understood and under-recognized. We report a case of a 61-year-old gentleman who presented with NSTE-ACS and was found to have SCAD. Patient Presentation: A 61-year-old male with history of untreated hyperlipidemia presented with acute substernal chest pressure radiating to bilateral arms and back. On presentation, vitals and physical examination was normal.His labs showed troponin I at 0.015 ng/mL which later up trended to 21.7 ng/ml. ECG demonstrated sinus bradycardia with no ischemic changes. Decision was made to take him for cardiac catheterization.It demonstrated right coronary artery (RCA) was ecstatic. Distally, there was a a right conus branch fistula draining into pulmonary artery. There was evidence of microvascular dysfunction. An echocardiogram showed mid and basal inferolateral akinesis, normal EF.He was started on dual anti platelets (DAPT) and GDMT. At the time of discharge, he started having recurrence of his chest pain with exertion. Cardiac CT showed multiple spontaneous coronary artery dissections with healing dissections and remodeling throughout the ecstatic RCA and its distal branches with additional contour irregularities and non-obstructive dissection flaps in the diagonal branch of the left anterior dissecting artery. He was enrolled into cardiac rehabilitation. Conclusion: SCAD occurs by the formation of an intramural hematoma or intimal disruption causing a coronary obstruction. Coronary angiography remains the primary tool in the diagnosis. Alternative imaging modalities, such as intravascular ultrasound and optical coherence tomography, CT coronary angiography can be used to confirm the diagnosis. It is managed medically with DAPT and adequate control of blood pressure. Cardiac rehabilitation appears to be beneficial in preventing recurrence. We would also like to emphasize that SCAD can occur in any age group and gender, it’s crucial to recognize it early and is a condition that can be managed conservatively.
Abstract 11933: Cardiac and Fibrosis-Related Biomarker Levels Do Not Predict Disease Development in Presymptomatic Phospholamban Cardiomyopathy
Authors: Remco de Brouwer, Wouter P te Rijdt, Herman H Sillje, Moniek G Cox, Rudolf A De Boer, Maarten P van den Berg
Journal: Circulation (2022)

Introduction: Phospholamban (PLN) cardiomyopathy is an inherited cardiomyopathy with malignant arrhythmias and/or heart failure due to fibrosis. There is no proven treatment against disease progression. The i-PHORECAST trial investigated whether the antifibrotic properties of eplerenone prevent disease development in presymptomatic mutation carriers using late gadolinium enhancement (LGE) as a measure of cardiac fibrosis. As part of this study, several biomarkers linked to cardiac damage and fibrosis were measured to investigate their prognostic use. Hypothesis: We assessed if biomarkers linked to cardiac damage and fibrosis enable early detection of overt PLN cardiomyopathy. Methods: Presymptomatic PLN mutation carriers (N=84, age 39 [27-50] years, 44% male) were randomized to receive eplerenone or no treatment. Biomarkers (NT-pro-BNP, troponin, TP1NP, GDF-15, and IL-6) were measured from blood samples at baseline (N=84) and after a three year follow up (N=57, age 37 [26-46] years, 49% male). Composite endpoints included changes in LVEDV/RVEDV/LVEF/RVEF, new LGE, QRS voltage, symptoms requiring treatment, ventricular ectopy, and cardiovascular death. Results: No clinically relevant and statistically significant differences between treatment groups, Table 1 . No significant association between baseline biomarker measurements and LVEF decrease or the development of new LGE, Figure 1 . Conclusions: Levels of NT-pro-BNP, troponin, TP1NP, GDF-15, and IL-6 are not associated with development of cardiac fibrosis or left ventricular dysfunction in presymptomatic PLN mutation carriers, thus do not enable early detection of overt PLN cardiomyopathy.
Abstract 12595: De Novo Lymphoproliferative Disorders in Heart Transplant Recipients: Predictors and Clinical Outcomes
Authors: Sang Hyun Kim, In-cheol Kim, Joseph W Rossano, Seonhwa Lee, Hyungseop Kim, Jin-jin Kim, Mi-Hyang Jung, Wida S Cherikh, Gabriel Vece, Josef Stehlik, Jong-Chan Youn
Journal: Circulation (2022)

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, clinical characteristics and predictors of PTLD in the real world have not been well studied. Methods We retrospectively analyzed clinical characteristics, predictors, and outcomes of PTLD, in 28,136 recipients of heart alone transplants between January 2000 and June 2015 from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry. Results Ten-year incidence of PTLD after successful discharge from HTx during 2000-2007 was 3.8%. The adjusted overall risk of mortality was significantly higher in patients diagnosed with PTLD within 3 years after HTx compared to those without PTLD (HR 2.22, 95% CI 1.86-2.65, p&lt;0.001). Bimodal age peak of the PTLD incidence within the 3 years of HTx and mortality after the diagnosis of PTLD was noted. Both adjusted risk of PTLD incidence and mortality were lower in recent HTx; lower incidence and mortality in era of 2008-2015, compared to 2000-2007 (Incidence: HR 0.75, 95% CI 0.57-0.98, p=0.038) (Mortality: HR 0.86, 95% CI 0.81-0.91, p&lt;0.001). Age at transplant, male recipient, high risk Epstein-Barr virus (EBV) mismatch (donor positive and recipient negative for EBV) were independent risk factors, while primary maintenance therapy with cyclosporine (vs. tacrolimus) at initial discharge was a protective factor for PTLD within 3 years. Conclusions The incidence as well as mortality of PTLD has decreased in recent years of HTx, possibly with advances in changed pattern of immunosuppression according to patient profile. Clinical characteristics such as age, male gender, EBV status and rejection history are key factors for assessing the risk of PTLD, which can be detrimental in the course of post HTx care.
Abstract 11198: Intra-Myocardial Dissecting Haematoma Presented as a Ventricular Tachycardia in a Patient With Remote Silent Myocardial Infarction
Authors: Noreena Iqbal, Yasmin Kamel, Attila Kardos
Journal: Circulation (2022)

Intramyocardial dissecting haematoma (IMDH), a rare form of myocardial rupture, is recognised as a complication of acute myocardial infarction (MI) but can also occur as a result of a thoracic trauma or spontaneous rupture of intramural coronary vessels. Before the advent of advanced multi-modality cardiac imaging, IMDH was an autopsy diagnosis. In this report, we present a patient with recent onset of palpitation due to non-compromising ventricular tachycardia (VT). Post cardioversion ECG showed anterior-apical deep Q waves in keeping with prior silent MI. Transthoracic echocardiography showed severely reduced left ventricular ejection fraction due to extensive apical aneurysm and raised the possibility of protruding apical thrombus. Subsequent contrast echocardiography showed features compatible with extensive LV apical thrombus and raised the differential diagnosis of contained myocardial rupture and IMDH. During the two years follow-up guideline directed medical therapy for heart failure and antiarrhythmic medication stabilised patient at NYHA class I-II with no recurrence of VT. Multimodality imaging including cardiac CT and MRI confirmed the suspicion of IMDH. With this case we are highlighting the difficulties in the diagnosis and the controversies of the management of IMDH. Figure: A: ECG shows monomorphic VT. B: after chemical cardioversion, ECG shows sinus rhythm with old transmural extensive anterior MI. C: Transthoracic echocardiography, apical 4 chamber view shows aneurysmatic left ventricular apex with echo lucent space with mobile intraventricular membrane separating the true LV lumen and the dissecting hematoma (Asterix). D: Contrast enhanced echocardiography delineating the true LV cavity from the IMDH. E,F: Contrast enhanced CT showing the low attenuation hematoma located in the anterior LV apex. Note the calcification in the LV apical myocardium indication of prior transmural MI.
Abstract 12466: Assessment of Extracellular Matrix Remodeling Biomarkers Shortly After Admission for ST-Elevated Myocardial Infarction
Authors: Elisavet Angeli, Alexander Reese-Petersen, Martin Frydland, Federica Genovese, Christian Hassager
Journal: Circulation (2022)

Introduction: ST-elevated myocardial infarction (STEMI) is followed by changes in the extracellular matrix (ECM) composition. ECM protein fragments are released into the bloodstream and can be targeted as biomarkers. We aimed at investigating the prognostic ability of ECM biomarkers in STEMI patients. Methods: Biomarkers of collagens type I, III, IV degradation (C1M, C3M, C4M, respectively) and collagen type VI formation (PRO-C6) were measured by specific enzyme-linked immunosorbent assays in plasma of 221 patients admitted with STEMI. Plasma was collected at two timepoints, at admission and 6-12 hours post-admission. The prognostic ability of the biomarkers was evaluated via Cox-proportional hazard regression analyses using all-cause mortality at 1 year as outcome. Results: The plasma concentration of all biomarkers significantly increased (15.5-28.4%) from admission to 6-12 hours post-admission (p&lt;0.0001). All biomarkers were prognostic for all-cause mortality within the first year after STEMI, after adjustment for potential risk factors (age, BMI, sex, blood pressure and smoking status) (Table 1). When applying a forward hazard regression analysis including the risk factors and the four ECM biomarkers at admission, PRO-C6 and C1M remained significantly associated with all-cause mortality at 1 year (C1M: HR=1.02, p-value=0.004, PRO-C6: HR=1.08, p-value=0.03). While after 6-12 hours, only C1M remained significantly associated (C1M: HR=1.04, p-value&lt;0.0001). Conclusions: Biomarkers reflecting degradation of collagens type I, III and IV, and formation of collagen type VI, were significantly altered shortly after admission for STEMI. PRO-C6 and C1M demonstrated an independent prognostic ability of risk of all-cause mortality within the first year after a STEMI event.